Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE
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OBJECTIVE: The Sydney classification criteria for antiphospholipid syndrome include lupus anticoagulant or moderate-to-high titre anticardiolipin IgG or IgM. We explored the association of all anticardiolipin isotypes, lupus anticoagulant and the combination with venous and arterial thrombosis. METHODS: Patients with systemic lupus erythematosus (SLE) in a large clinical cohort seen quarterly were repeatedly tested by protocol for anticardiolipin antibodies and lupus anticoagulant. Subgroups of patients were defined based on the geometric mean titres of IgG, IgM, IgA anticardiolipin and lupus anticoagulant expressed in dilute Russell's viper venom time (RVVT) seconds for each patient across all cohort visits. These subgroups were compared with respect rates of thrombosis since diagnosis with SLE. Rate ratios were estimated using Cox Proportional Hazards models. RESULTS: Of the 1390 cohort members included, there were 284 thrombotic events observed over 17 025 person-years since diagnosis for a rate of 1.7 events per 100 person-years. Those with a geometric mean titre of IgG anticardiolipin >20 had a significantly elevated rate of thromboses (rate ratio 1.8, p=0.0052), whereas there was no evidence of an association between thromboses and elevated IgM geometric mean (rate ratio 1.2, p=0.40). There were relatively few cohort members with elevated IgA geometric mean but the rate of thromboses in that group was elevated (rate ratio 1.7, p=0.23). The associations between anticardiolipin antibodies and thromboses were strongest when considering venous thromboses. Those with two or more elevated anticardiolipin isotypes or those with both IgG anticardiolipin and RVVT did not appear at higher risk than those with a single elevated marker. CONCLUSION: This study supports previous observations that IgG anticardiolipin and lupus anticoagulant are associated with higher rates of thromboses. Our power to study IgA anticardiolipin was limited due to small number of patients with elevated IgA.
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Large studies found that IgM aCL and IgM anti-β2-glycoprotein I are not associated with thrombotic events.
“Large studies found that IgM aCL and IgM anti-β2-glycoprotein I are not associated with thrombotic events [9–13].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [10]
The Results report no evidence of an association between elevated IgM anticardiolipin (aCL) and thrombosis in a cohort of 1,390 people with SLE. The paper does not report a thrombosis finding for IgM anti-β2-glycoprotein I, so it supports only the IgM aCL part of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredElevated titres of IgA isotypes have been shown to be associated with thrombosis.
“Moreover, elevated titres of IgA isotypes have been shown to be associated with thrombosis [10, 14–16].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [10]
The Discussion reports higher thrombosis rates among SLE patients with elevated IgA anticardiolipin, but says the increased risk in this cohort was not statistically significant. The unqualified claim overstates what this study establishes, although the Discussion also reports a significant association found by another study. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIgM aCL is not associated with lifetime thrombosis risk in SLE.
“Moreover, it has been shown that IgM aCL is not associated with lifetime thrombosis risk in SLE [10, 11].”
From Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus (2021) · cites this paper as [10]
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- [13]Somers E, Magder L, Petri M Antiphospholipid Antibodies and incidence of venous thrombosis in a cohort of patient with Systemic Lupus Erythematosus. J Rheumatol 2002; 29: 2531– 6. 12465147
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Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus
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Self-citation
- Authors
- Domingues, V., Magder, L. S., & Petri, M.
- Affiliations
- New York University (US)
- University of Maryland, Baltimore (US)
- Johns Hopkins University (US)
- Corresponding author
- Petri, Michelle
- Venue
- Lupus Science & Medicine
- Publisher
- BMJ
- Published
- 2016-06
- Volume
- 3
- Issue
- 1
- Pages
- e000107
- ISSN
- 2053-8790 (ISSN-L)
- PMC
- PMC4932305
- OpenAlex
- W2467830678
- Cited by
- 36
- References
- 27
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 3 · 2018: 1 · 2017: 3
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Lupus Science & Medicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043727)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- anticardiolipin antibodies, lupus anticoagulant, systemic lupus erythematosus, thrombosis, venous thrombosis, arterial thrombosis, antiphospholipid syndrome, dilute Russell's viper venom time, antibody titers
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